维生素D受体起始密码子基因多态性与系统性红斑狼疮相关性研究

目的 检测维生素D受体(VDR)基因多态性在系统性红斑狼疮(SLE)患者中的分布,探讨其与SLE发病的相关性.方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析技术检测VDR起始密码子(FokI)多态性位点和基因型在271例SLE患者和130名健康对照组中的分布情况.采用χ2检验和方差分析进行统计学处理.结果 SLE患者及健康对照组VDR FokI多态性基因型和等位基因分布均不处于Hardy-Weinberg平衡(SLE组χ2=7.883,P=0.019;健康对照组:χ2=7.288,P=0.026).VDR FokI多态性等位基因F和f的分布频率在健康对照组分别为48.8%和51.2%,在SLE组分别为60.9%(χ2=10.39,P=0.001)和39.1%(χ2=10.39,P=0.001);F等位基因个体发生SLE的比值比(OR)为1.630(95%CI=1.210～1.1%,χ2=10.39,P=0.001).基因型FF、Ff和ff分布频率在健康对照组中分别为25.4%、46.9%和27.7%,在SLE组中分别为42.8%(χ2=11.417,P=0.001)、36.2(χ2=4.251,P=0.039)和21.0%(χ2=2.187,P=0.139);FF和Ff基因型个体发生SLE的OR分别为2.200(95%CI=1.385～3.493,χ2=11.417,P=0.001)和0.641(95%C1=0.419～0.979,χ2=4.251,P=0.039).进一步分析发现,不同VDR FokI多态性基因型SLE患者之间疾病活动性积分(SLEDAI)差异无统计学意义(P=0.382).但与FF和ff基因型SLE患者对照,Ff基因型SLE患者中浆膜炎的发生率更高(P=0.001),而且具有更高阳性率的抗双链DNA(dsDNA)抗体(P=0.001)、抗Sm抗体(P=0.047)和抗组蛋白抗体(P=0.001),但皮疹发生率较低(P=0.005).结论 VDR FokI多态性位点F等位基因和F/F及F/f基因型与SLE发病易感性有关,而且F/f杂合子患者更容易发生浆膜炎和产生抗dsDNA抗体、抗Sm抗体和抗组蛋白抗体.

Association of vitamin D receptor gene FokI polymorphism with systemic lupus erythematosus

Objective To determine the distribution of vitamin D receptor(VDR)gene FokI polymorphism in systemic lupus erythematosus(SLE)and the association with SLE in Chinese Han patients. Methods Genomic DNA from 271 Chinese SLE patients and 130 sex and ethnically matched controls were typed for VDR FokI polymorphism by polymerase chain reaction restriction fragment length polymorphism(PCRRFLP). Clinical characteristics were analyzed between different FokI genotypes. ResuIts Fokl allelic frequencies were not in Hardy-Weinberg equilibrium(χ2=7.288, P=0.026 for the control group and χ2=7.883, P=0.019 for the SLE patient group). The distribution frequencies of allelic gene F and f were 48.8% and 51.2% in the controls respectively, 60.9% and 39.1%(χ2=10.39, P=0.001)in the SLE patients respectively. The relative risk of allelic gene F developing to SLE was 1.630(95%CI=1.210～1.196, χ2=10.39, P=0.001). The distribution frequencies of genotypes homozygote FF, heterozygote Ff and homozygote ff were 25.4%, 46.9%,and 27.7% in the controls respectively; 42.8%(χ2=11.417, P=0.001), 36.2%(χ2=4.251, P=0.039)and 21.0% (χ2=2.187, P=0.139)in SLE respectively. The relative risk of homozygote FF and heterozygote Ff genotypes was 2.200(95%CI=1.385～3.493, χ2=11.417, P=0.001)and 0.641(95%CI=0.419～0.979, χ2=4.251, P=0.039)respectively. Furthermore, no significant difference was observed in SLE patients carrying different FokI genotypes in SLE disease activity index(SLEDAI)(P=0.382), symptoms and signs, while significant difference was observed in SLE patients carrying heterozygote Ff genotypes involved in serositis(P=0.001). Elevated frequencies of heterozygote Ff genotypes were observed in patients with anti-dsDNA antibody, anti-Sm antibody and anti-histone antibody respectively(P=0.001, P=0.047, P=0.001 respectively). However, the incidence rate of malar rash was lower than other genotypes in heterozygote Ff genotypes(P=0.005).Conclusion There is association between the VDR gene FokI polymorphism and the susceptibility to systemic lupus erythematosus in Han population of southern China. Allelic gene F, homozygote FF and heterozygote Ff genotypes increase the susceptibility to systemic lupus erythematosus. Otherwise, heterozygote Ff genotype is more frequently involved in serositis and generates anfi-dsDNA antibody, anti-Sm antibody and anti-Histone antibody.